FGFR3-TACC3 fusion

Recently, Khan and colleagues thoroughly characterized a recurrent FGFR3-TACC3 fusion caused by HPV integration in oropharyngeal squamous cell carcinoma (OPSCC) identifying synergistic interplay with HPV E6/E7 required for transformation. These findings reveal another mechanism in which virus integration can ignite tumorigenesis and a promising avenue for future investigation.

For adults with tumors with histopathological features of PLNTY, further molecular and methylation analyses are needed for grading. If TERT promoter mutations are present, even with a PLNTY methylation profile, these tumors can still exhibit the biological behavior of high-grade gliomas.

Safety was consistent with the overall FIGHT-207 population. Pemigatinib had antitumor activity and a manageable safety profile in patients with CNS tumors.

Erdafitinib (47.37%) was the most frequently used FGFRi drug in clinical studies...In conclusion, UC patients with FGFR3 fusions, especially FGFR3-TACC3 fusions, may benefit more from FGFRi than those with FGFR3 mutations, which highlighted the importance of FGFR3 alteration site test in determining the efficacy of FGFRi-based therapy and enhanced the patient benefit for FGF/FGFR-altered UC. Future studies with larger sample size and individual patient data are needed to confirm these findings and explore the underlying mechanisms of the differential response to FGFRi.

Functionally, FGFR inhibitors ameliorated PD1/PD-L1-mediated T cell suppression in co-culture assays. Together, these findings highlight a novel mechanism by which FGFR inhibitors suppress IFN-γ-induced PD-L1 via autophagy and suggest a potential strategy to improve ICI therapy in FGFR3-altered NMIBC.

Erdafitinib was approved for the treatment of UC but is limited by the progression of on-target gatekeeper resistance mutations...In FGFR3-TACC3 fusion-positive cells, LC-MF-4 exerted its effects by suppressing the expression of genes involved in mitochondrial biogenesis and ATP synthesis. This study demonstrated robust antitumor activity of LC-MF-4 in the Ba/F3-FGFR3-TACC3 xenograft model, highlighting its potential for the treatment of FGFR3-altered cancers.

FGFR3-TACC3 expression decreased the ubiquitination and degradation of E6 and E7, thereby increasing oncoprotein abundance. We conclude that expression of HPV16 oncoproteins and host gene fusions generated from HPV integration sites can be sufficient for cancer development.

F3-T3 facilitates the proliferation, invasion, migration and EMT of glioma cells, thereby promoting their malignant progression through STAT3 signaling activation. These findings highlight its potential as a therapeutic target for glioma treatment.

Despite major progress in biotechnology, our understanding on the role of fusion events in glioblastoma represented by the FGFR-TACC is still in its infancy. Here, we highlight recent progress on FGFR-TACC fusion in human glioblastoma, emphasizing their molecular mechanisms and potential clinical value.

Both FGF PV and KRAS are the independent factors for poor prognosis. To our knowledge, this is the first report to describe an inflamed microenvironment recruited by NOTCH1/RB1 co-mutation, indicating potential benefit from immunotherapy.

This study revealed that one in eight a/m UC patients had FGFR2/3 GAs, and a few changes were observed in FGFR GA status before and after treatment. Genetic testing will be beneficial for the selection of appropriate treatments after a diagnosis of a/m UC.

In vivo tumor models corroborated these findings, demonstrating a significantly diminished tumor volume in the Cas13a-treated cohort relative to both the control and shRNA-treated groups. The CRISPR-Cas13a gene-editing system has been demonstrated to significantly suppress tumor proliferation both in vitro and in vivo, thereby presenting itself as a promising candidate for a novel and efficacious therapeutic intervention in bladder cancer treatment.